It has been previously shown that MHC restricted cytotoxic T lymphocytes recognize foreign antigen in the form of short peptides. In defining the minimal requirements for the induction of virus specific CTL, a peptide containing epitopes from the influenza type A matrix (M1) protein recognized by both human CTL and T helper cells has been shown to sensitize target cells for recognition by influenza A virus specific CTL. This peptide was also shown to induce cytolytic effector cells from human peripheral blood lymphocytes (PBL) when cultured with the PBL even in the absence of exogenous growth factors. These data indicate that virus specific CTL can be stimulated in vitro with the CTL epitope and the lymphocytes secreted by the T helper cells induced by the T helper cell epitope. This information will be important for the design of synthetic peptide based vaccines for the production of CTL mediated immunity. To defined the parameters of interaction of viral peptide antigens with MHC class I molecules, it was necessary to define peptide antigens recognized in the context of H-2 class I molecules available in soluble form i.e. H-2Kb and H-2Dd. The influenza A virus basic polymerase 2 (PB2) was found to be recognized by H-2Dd restricted influenza virus specific CTL, and of the thirty one peptides synthesized, three peptides from PB2 were found to be recognized by the virus specific CTL. These CTL epitopes have low amphipathicity values, but fit the Rothbard algorithm for T cell epitopes. The peptides that have been identified have been radiolabeled and the MHC molecule binding studies have begun. In addition, four epitopes recognized by SV40 specific, H-2Db restricted CTL have been identified and studies on H-2Db are in progress.